The Role of C-Reactive Protein as a Triage Tool for Pulmonary Tuberculosis in Children

Abstract

Background: C-reactive protein (CRP) has shown promise as a triage tool for pulmonary tuberculosis (TB) in adults living with the human immunodeficiency virus. We performed the first assessment of CRP for TB triage in children.

Methods: Symptomatic children less than 15 years old were prospectively enrolled in Kampala, Uganda. We completed a standard TB evaluation and measured CRP using a point-of-care assay. We determined the sensitivity and specificity of CRP to identify pulmonary TB in children using 10 mg/L and 5 mg/L cut-off points and generated a receiver operating characteristic (ROC) curve to determine alternative cut-offs that could approach the target accuracy for a triage test (≥90% sensitivity and ≥70% specificity).

Results: We included 332 children (median age 3 years old, interquartile range [IQR]: 1-6). The median CRP level was low at 3.0 mg/L (IQR: 2.5-26.6) but was higher in children with Confirmed TB than in children with Unlikely TB (9.5 mg/L vs. 2.9 mg/L, P-value = .03). At a 10 mg/L cut-off, CRP sensitivity was 50.0% (95% confidence interval [CI], 37.0-63.0) among Confirmed TB cases and specificity was 63.3% (95% CI, 54.7-71.3) among children with Unlikely TB. Sensitivity increased to 56.5% (95% CI, 43.3-69.0) at the 5 mg/L cut-off, but specificity decreased to 54.0% (95% CI, 45.3-62.4). The area under the ROC curve was 0.59 (95% CI, 0.51-0.67), and the highest sensitivity achieved was 66.1% at a specificity of 46.8%.

Conclusions: CRP levels were low in children with pulmonary TB, and CRP was unable to achieve the accuracy targets for a TB triage test.

Keywords: C-reactive protein; child; triage; tuberculosis.

Figure 1.

Participant flowchart.

Figure 2.

Distribution of C-reactive protein levels by pediatric TB classification. Density plot of each C-reactive protein (CRP) level plotted by TB status of Confirmed, Unconfirmed, or Unlikely TB.

Figure 3.

Receiver operating characteristic (ROC) curves for C-reactive protein to diagnose childhood TB. ROC Curves for three reference standards: Confirmed TB versus Unlikely TB, composite reference standard (CRS), and microbiological reference standard (MRS). The gray-dashed lines indicate the target accuracy for a triage test for TB (≥90% sensitivity and ≥70% specificity), and the red-dashed line is the reference line with an area under the curve (AUC) of 0.5.